Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome–positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome–negative–/BCR-ABL1–positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P < .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade ≥ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.

中文翻译：

---

博舒替尼与伊马替尼治疗新诊断的慢性粒细胞白血病：随机 BFORE 试验的结果

目的 Bosutinib 是一种有效的双重 SRC/ABL 激酶抑制剂，批准用于对先前治疗耐药和/或不耐受费城染色体阳性慢性髓细胞白血病 (CML) 的成人。我们评估了博舒替尼与伊马替尼一线治疗慢性期 CML 的疗效和安全性。方法 在这项正在进行的多国 III 期研究中，536 名新诊断为慢性期 CML 的患者以 1:1 的比例随机分配接受每天一次 400 mg 波舒替尼（n = 268）或伊马替尼（n = 268）。根据方案，在具有典型（e13a2/e14a2）转录本（博舒替尼，n = 246；伊马替尼，n = 241）的费城染色体阳性患者中评估疗效。费城染色体阴性/BCR-ABL1 阳性状态的患者以及费城染色体状态未知和/或非典型 BCR-ABL1 转录物类型的患者被排除在该人群之外。结果 12 个月时（主要终点）的主要分子反应（MMR）率显着高于伊马替尼（分别为 47.2% 和 36.9%；P = 0.02），完全细胞遗传学反应（CCyR）率也高出 12个月（分别为 77.2% 和 66.4%；P = .0075）。博舒替尼的累积发病率有利（MMR：风险比，1.34；P = .0173；CCyR：风险比，1.38；P < .001），反应时间更早。接受波舒替尼治疗的 4 名患者 (1.6%) 和接受伊马替尼治疗的 6 名患者 (2.5%) 经历了疾病进展到加速/急变期。在接受治疗的患者中，22.0% 的患者接受波舒替尼治疗，26. 8% 接受伊马替尼的患者停止治疗，最常见的是药物相关毒性（分别为 12.7% 和 8.7%）。≥ 3 级腹泻 (7.8% v 0.8%) 和升高的 ALT (19.0% v 1.5%) 和 AST (9.7% v 1.9%) 水平在波舒替尼组中更为常见。心脏和血管毒性不常见。结论 接受波舒替尼治疗的患者的 MMR 和 CCyR 发生率显着高于接受伊马替尼治疗的患者，且反应更快。与已知的安全性一致，胃肠道事件和转氨酶升高更常见于波舒替尼。结果表明，博舒替尼可能是慢性期 CML 的有效一线治疗药物。5%) 和 AST (9.7% v 1.9%) 水平在波舒替尼组中更为常见。心脏和血管毒性不常见。结论 接受波舒替尼治疗的患者的 MMR 和 CCyR 发生率显着高于接受伊马替尼治疗的患者，且反应更快。与已知的安全性一致，胃肠道事件和转氨酶升高更常见于波舒替尼。结果表明，博舒替尼可能是慢性期 CML 的有效一线治疗药物。5%) 和 AST (9.7% v 1.9%) 水平在波舒替尼组中更为常见。心脏和血管毒性不常见。结论 接受波舒替尼治疗的患者的 MMR 和 CCyR 发生率显着高于接受伊马替尼治疗的患者，且反应更快。与已知的安全性一致，胃肠道事件和转氨酶升高更常见于波舒替尼。结果表明，博舒替尼可能是慢性期 CML 的有效一线治疗药物。